Evaluation of acute and subacute toxicity of hydroethanolic extract of Dolichandra unguis-cati L. leaves in rats.

Dolichandra unguis-cati L. is a native climbing plant of Brazil, popularly known as "unha de gato". It has been traditionally used mainly as an antipyretic, anti-inflammatory and anti-tumor agent, yet little toxicological information is found in the literature. To identify the chemical composition of the hydroethanolic extract obtained from the leaves of Dolichandra uniguis-cati and to evaluate the acute and subacute toxicity in male and female rats, in order to assess the safety profile of this plant. In the acute study, a single dose (2000mg/kg) of the extract was orally administered to male and female rats. In the subacute study, the extract was orally administered to male and female rats at doses 100, 200 and 400mg/kg for 28 days. Behavioral changes, catalase and tbars evaluations, biochemical, hematological and histopathological analysis were determined. The extract' chemical composition was accessed through UHPLC/MS. Chlorogenic acid, caffeic acid, ferulic acid, vanillinic acid, p-coumaric acid, rosmarinic acid, trans-cinnamic acid, luteolin, apigenin, quercitrin and quercetin were identified in the extract. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. In relation to the subacute study, females showed a reduction in AST (100, 200 and 400mg/kg), ALT (200mg/kg) and BUN (100 and 200mg/kg) levels, while male rats 400mg/kg presented an increase in AST levels. The Chol dosage significantly decreased in female rats in a dose-dependent manner, whereas for male rats this parameter showed no statistically significant reductions. No behavioral and histopathological changes were recorded. Our results indicate that the hydroethanolic extract of Dolichandra unguis-cati leaves did not present relevant toxic effects when administered orally to male and female rats. The extract also showed a potential hypocholesterolemic activity.

Calil Brondani J ，Reginato FZ ，da Silva Brum E ，de Souza Vencato M ，Lima Lhamas C ，Viana C ，da Rocha MI ，de Freitas Bauermann L ，Manfron MP ... -  《-》

Acute and subacute toxicity and chemical constituents of the hydroethanolic extract of Verbena litoralis Kunth.

Verbena litoralis Kunth is a native species of South America, popularly known as gervãozinho-do-campo or erva-de-pai-caetano. It is used in gastrointestinal disorders, as detoxifying the organism, antifebrile properties and amidaglitis. To identify the chemical constituents of the hydroethanolic extract obtained from the aerial parts of V. litoralis and to evaluate the acute and sub-acute toxicity in male and female rats. The single dose (2000 mg/kg) of the extract was administered orally to male and female rats. In the subacute study the extract was given at doses of 100, 200 and 400 mg/kg during 28 days orally. Biochemical, hematological and histological analyzes were performed, oxidative stress markers were tested and chemical constituents were identified through UHPLC-ESI-HRMS RESULTS: Six classes of metabolites were identified: iridoids glycosides, flavonoids, phenylpropanoids-derived, phenylethanoid-derived, cinnamic acid-derived and triterpenes. In the acute treatment, the extract was classified as safe (category 5), according to the OECD guide. Our results demonstrated that subacute administration of the crude extract of V. litoralis at 400 mg/kg resulted in an increase in AST in males, whereas ALT enzyme showed a small increase in males that received 200 mg/kg and 400 mg/kg of the extract. The extract of the aerial parts of Verbena litoralis did not present significant toxicity when administered a single dose. However, when different doses were administered for 28 days, were observed changes in hematological, biochemical and histological parameters in rats.

de Lima R ，Guex CG ，da Silva ARH ，Lhamas CL ，Dos Santos Moreira KL ，Casoti R ，Dornelles RC ，da Rocha MIUM ，da Veiga ML ，de Freitas Bauermann L ，Manfron MP ... -  《-》

Safety assessment of Morus nigra L. leaves: Acute and subacute oral toxicity studies in Wistar rats.

Morus nigra L. is a plant native to Asia, and well adapted to the Brazilian climate. It is popularly known as "amoreira preta", and is part of the National List of Plants of Interest to the Brazilian Unified Health System. It is used in folk medicine mainly to soften the effects of menopause, as anti-inflammatory, antidiabetic and antihypertensive. However, information on safe doses and use is still precarious. To identify the chemical composition of the ethanolic extract of Morus nigra L. leaves (EEMN), as well as perform a toxicological study in male and female rats. The chemical composition of the extract was performed by HPLC/DAD. In the acute study, the dose administered was 2000 mg/kg, and signs of toxicity and mortality was observed. In the sub-acute study, the extract was administered at doses of 500, 750 and 1000 mg/kg for 28 days. Behavioral changes, object recognition test, renal and hepatic tissue assessments, biochemical and hematological parameters were determined. The extract was administered orally to male and female rats in both studies. Quercetin and caffeic acid showed as major compounds in the extract. In the acute treatment, the extract was classified as safe (category 5), according to the protocol. In the subacute study, there was a decrease in AST in males (750 and 1000 mg/kg) and females (1000 mg/kg), reduction of total cholesterol in females (750 and 1000 mg/kg), and increase in renal and hepatic change the LPO levels. The present investigation showed that EEMN did not present significant toxic effects when administered orally. Moreover, presented a potentially protective action of organs and possesses hypocholesterolemic activity, thus, it is shown as a promising natural source to be used in pharmacology.

Figueredo KC ，Guex CG ，Reginato FZ ，Haas da Silva AR ，Cassanego GB ，Lhamas CL ，Boligon AA ，Lopes GHH ，de Freitas Bauermann L ... -  《-》

Biochemical and hematological effects of acute and sub-acute administration to ethyl acetate fraction from the stem bark Scutia buxifolia Reissek in mice.

Scutia buxifolia is a native tree of Southern Brazil, Uruguay, and Argentina, which is popularly known as "coronilha" and it is used as a cardiotonic, antihypertensive and diuretic substance. The aim of this study was to assess the acute and sub-acute toxicity of the ethyl acetate fraction from the stem bark Scutia buxifolia in male and female mice. The toxicity studies were based on the guidelines of the Organization for Economic Cooperation and Development (OECD-guidelines 423 and 407). In an acute study, a single dose of 2000 mg/kg of Scutia buxifolia was administered orally to male and female mice. Mortality, behavioral changes, and biochemical and hematological parameters were evaluated. In the sub-acute study, Scutia buxifolia was administered orally to male and female mice at doses of 100, 200, and 400mg/kg/day for 28 days. Behavioral changes and biochemical, hematological, and histological analysis were evaluated. The acute administration of Scutia buxifolia did not cause changes in behavior or mortality. Male and female mice presented decreased levels of platelets. Female mice presented decreased levels of leukocytes. On the other hand, in a sub-acute toxicity study, we observed no behavioral changes in male or female mice. Our results demonstrated a reduction in glucose levels in male mice treated to 200 and 400mg/kg of Scutia buxifolia. Aspartate aminotransferase (ASAT) activity was increased by Scutia buxifolia at 400mg/kg in male mice. In relation to the hematological parameters, male mice presented a reduction in hemoglobin (HGB) and hematocrit (HCT) when treated to 400mg/kg of plant fraction. Female mice showed no change in these parameters. Histopathological examination of liver tissue showed slight abnormalities that were consistent with the biochemical variations observed. Scutia buxifolia, after acute administration, may be classified as safe (category 5), according to the OECD guide. However, the alterations observed, after sub-acute administration with high doses of ethyl acetate fraction from the stem bark Scutia buxifolia, suggest that repeated administration of this fraction plant can cause adverse hepatic, renal, and hematological effects.

da Silva AR ，Moreira Lda R ，Brum Eda S ，de Freitas ML ，Boligon AA ，Athayde ML ，Roman SS ，Mazzanti CM ，Brandão R ... -  《-》

Antidiabetic effects of Olea europaea L. leaves in diabetic rats induced by high-fat diet and low-dose streptozotocin.

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance, and dyslipidemia. It has broad occurrence worldwide, affecting millions of people, and can cause serious complications. The olive (Olea europaea L.) has important pharmacological functions, including anti-inflammatory, antioxidant, and hypoglycemic activities. Olive leaves are used in traditional medicine for diabetes and hypertension. To evaluate the effect of the ethanolic extract of olive leaves (EEOL) on the metabolism of rats with diabetes induced by a high-fat diet and low dose of streptozotocin (STZ). Male Wistar rats were either given normal feed or a high-fat diet (70% standard laboratory feed, 15% sucrose, 10% lard and 5% yolk powder) for four weeks, followed by administration of STZ (35 mg/kg, via ip). Animals with fasting glucose levels above 200 mg/dL were considered diabetic. Animals were divided into 5 groups, which received ethanol (10 mL/kg), metformin (250 mg/kg), or EEOL at doses of 200 and 400 mg/kg during 10 weeks by oral gavage. Blood samples were used to measure hematological and biochemical parameters, and kidneys were removed for posterior analysis. Body weight was recorded weekly. A significant decrease in body weight was observed among diabetic animals treated with ethanol and EEOL compared to the control group. Moreover, animals treated with EEOL showed an improvement in glucose levels and in levels of inflammatory and metabolic markers when compared to diabetic animals. The results indicate a potential anti-diabetic activity of olive leaves, however more studies are needed to validate clinical effects.

Guex CG ，Reginato FZ ，de Jesus PR ，Brondani JC ，Lopes GHH ，Bauermann LF ... -  《-》